3D kidney organoids for bench-to-bedside translation
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REVIEW
3D kidney organoids for bench-to-bedside translation Navin Gupta✉ 1,2,3 & Emre Dilmen 1 & Ryuji Morizane 1,2,3,4 Received: 17 April 2020 / Revised: 30 June 2020 / Accepted: 22 September 2020 # The Author(s) 2020
Abstract The kidneys are essential organs that filter the blood, removing urinary waste while maintaining fluid and electrolyte homeostasis. Current conventional research models such as static cell cultures and animal models are insufficient to grasp the complex human in vivo situation or lack translational value. To accelerate kidney research, novel research tools are required. Recent developments have allowed the directed differentiation of induced pluripotent stem cells to generate kidney organoids. Kidney organoids resemble the human kidney in vitro and can be applied in regenerative medicine and as developmental, toxicity, and disease models. Although current studies have shown great promise, challenges remain including the immaturity, limited reproducibility, and lack of perfusable vascular and collecting duct systems. This review gives an overview of our current understanding of nephrogenesis that enabled the generation of kidney organoids. Next, the potential applications of kidney organoids are discussed followed by future perspectives. This review proposes that advancement in kidney organoid research will be facilitated through our increasing knowledge on nephrogenesis and combining promising techniques such as organ-on-achip models. Keywords Kidney organoid . Stem cells . Bioengineering . Nephron
Introduction Kidneys are essential organs that filter the blood to generate metabolic waste, destined for urinary excretion. The kidneys have remarkable plasticity in tailoring the composition of urine, matching intake with excretion to maintain solute homeostasis and fluid balance. As the mammalian kidney is a non-regenerative organ, loss of functional units, or nephrons, accumulates over time in all individuals [1]. Systemic diseases of high prevalence, namely, hypertension and diabetes Navin Gupta and Emre Dilmen contributing first authors * Navin Gupta✉ [email protected] Ryuji Morizane [email protected]; [email protected] 1
Nephrology Division, Massachusetts General Hospital, Boston, MA, USA
2
Department of Medicine, Harvard Medical School, Boston, MA, USA
3
The Wyss Institute, Harvard University, Cambridge, MA, USA
4
Harvard Stem Cell Institute, Cambridge, MA, USA
mellitus, medication or hemodynamic-induced acute kidney injury (AKI), and primary diseases of the kidney, are common causes for hastened loss of kidney function and comprise the major etiologies for chronic kidney disease (CKD) [2]. CKD is divided into stages based on kidney dysfunction, which causes solute derangements and fluid imbalance responsible for extensive morbidity and mortality. In the USA, CKD has a reported prevalence of 14% [3], has an annual treatment cost of $120 billion [4], negatively impacts quality of life [5], and at advanced stages culminates in end-stage renal disease (ESRD),
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